Children's Hospital Colorado

Endocrinology Research at Children's Hospital Colorado

About our Endocrinology Research Program

The Barbara Davis Center (with Children’s Hospital Colorado for inpatient pediatric diabetes care) follows 3,000 children and 2,000 adults with Type 1 diabetes. For the great majority, Type 1 diabetes is an autoimmune disease. We can now predict the development of Type 1 diabetes, prevent it in animal models and trials for prevention in man are underway.

The Center has pioneered the prediction of Type 1 diabetes, developing and using autoantibody assays targeting four major islet autoantigens (GAD65, IA-2, insulin, and most recently ZnT8). Given genetic susceptibility primarily determined by HLA alleles, individuals in the general population as well as relatives who express >=2 of the above autoantibodies progress to diabetes. Though autoantibodies are used for diagnosis of autoimmune diabetes and prediction of the disease, T cells cause the disease by killing cells in islets that produce insulin.

Studies of the NOD mouse model indicates that insulin is the primary target, and mutating a single amino acid of insulin peptide B:9-23, prevents diabetes (Nakayama et al, Nature 2005).  Major studies are directed at a trimolecular complex of HLA presenting molecule, insulin peptide, recognized by specific T cell receptors, which underlies disease pathogenesis. Structural characterization of trimolecular complexes targeting insulin peptides for man and mouse is being pursued to develop both T cell disease related biomarkers and develop specific immunotherapy.

Program point of contact

Katherine Gray